A detailed pathological, genetic and biochemical study of a disease of cattle now known as mannosidosis has provided (1) a valuable and readily available model inherited lysosomal storage disease, (2) a means of control of a practical veterinary problem by heterozygote detection. In mannosidosis there is storage of mannose containing oligosaccharides in lysosomes consequent to a deficiency of acid alpha-mannosidase. Heterozygous animals have a partial deficiency of this enzyme. Present work involves a continuation of the evaluation of various techniques of heterozygous testing using the large number of animals available to us in a population 10% of which are heterozygous. The various forms of acid alpha-mannosidase are being studied as a prelude to their purification and use in enzyme replacement experiments. The ability to examine the various problems of getting enzyme into various cells, its life in cells and its effectiveness against the storage material in various tissues in an expendable model should provide useful information not available from the empirical enzyme therapy of children or tissue culture work.